A comparative trial of controlled-onset, extended-release verapamil, enalapril, and losartan on blood pressure and heart rate changes

Abstract

Background The excess morning risk of myocardial infarction and stroke may be attributable to the rapid rise in blood pressure (BP) and heart rate in the hours after awakening. The aim of this randomized, double-blinded, placebo-controlled, multicenter study was to compare once-daily, controlled-onset, extended-release (COER-24) verapamil to enalapril and losartan on BP and heart rate during the postawakening morning phase as well as throughout the 24-h period. Methods A total of 406 patients were randomized to an 8-week forced-titration period with one of the following: 1) COER-24 verapamil 240 mg/day titrated to 360 mg/day; 2) enalapril 10 mg/day titrated to 20 mg/day, 3) losartan 50 mg/day titrated to 100 mg/day, or 4) placebo. Office BP and heart rate and ambulatory 24-h BP monitoring was performed at baseline, 4 weeks, and 8 weeks. Results Each active treatment, as compared with placebo, lowered BP both during the morning hours as well as the entire 24-h period. COER-24 verapamil was more effective in lowering morning systolic (−16.6 mm Hg) and diastolic (−11.9 mm Hg) BP than either enalapril or losartan ( P < .001). For the entire 24-h period, the effects of COER-24 verapamil (−11.6/−8.4 mm Hg) were comparable to enalapril (−13.4/−8.3 mm Hg; P = NS). Losartan achieved a similar 24-h effect on systolic pressure (−9.3 mm Hg) but was less effective on diastolic pressure (−5.4 mm Hg; P = .004 v COER-verapamil). Unlike losartan or enalapril, COER-24 verapamil was the only treatment to lower the heart rate over both the 24-h period (−4.6 beats/min; P < .001) and during waking hours (−4.6 beats/min; P < .001). A blunted rate of rise in BP, heart rate, and rate–pressure product occurred during the postawakening period with COER-verapamil ( P = .03) but not with either of the other treatment arms. Lastly, the decline in BP at night was similar for COER-verapamil and losartan and greater with enalapril ( P = .014) Conclusions COER-24 verapamil produces changes in BP and pulse that more closely match the normal circadian hemodynamic rhythms than either do enalapril or losartan.